Cold physical plasma, a partially ionized gas, has been shown to be effective in treating chronic wounds and cancer. However, there is limited research on plasma exposure of leukemia cell lines, such as chronic lymphocytic leukemia (CLL) and cytotoxic CD8+ T cells. To investigate the potential proimmunogenic effects of plasma‐derived reactive oxygen species, cytotoxic T cells were isolated from CLL patients and healthy volunteers. Extensive cold plasma treatment reduced T‐cell metabolic activity and viability in both diseased and healthy groups. Plasma treatment of cocultures, but not CD8+ T‐cell monocultures, spurred cytotoxic T‐cell proliferation, possibly due to plasma‐enhanced CLL antigen display and plasma‐mediated modulation of immunoregulatory surface molecules. Further studies are needed to understand the mechanisms and clinical relevance of these findings.